Deep psychophysiological phenotyping of adolescents and adults with 22q11.2 deletion syndrome: a multilevel approach to defining core disease processes

• Published in: BMC psychiatry 2023-06, Vol.23 (1), p.425-425, Article 425
• Main Authors: Parker, David A, Cubells, Joseph F, Imes, Sid L, Ruban, Gabrielle A, Henshey, Brett T, Massa, Nicholas M, Walker, Elaine F, Duncan, Erica J, Ousley, Opal Y
• Format: Article
• Language: English
• Subjects: (up to 10): 22q11.2DS; Acoustic startle; Acoustics; Adolescent; Adult; Adults; Analysis; Animal cognition; Attention deficit hyperactivity disorder; Autism; Autistic Disorder - diagnosis; Biomarkers; Care and treatment; Child; Child Development Disorders, Pervasive; Chromosomal instability syndromes; Chromosome Deletion; Cognition; Cognitive ability; Data collection; Deep phenotyping; Diagnosis; DiGeorge syndrome; DiGeorge Syndrome - diagnosis; Drug use; EEG; Electroencephalography; Humans; Information processing; Longitudinal Studies; Lymphocytes T; Mental disorders; Middle Aged; Neurodevelopmental disorders; Neurotransmission; Phenotype; Phenotypes; Phenotyping; Psychiatry; Psychosis; Psychotic Disorders; R&D; Research & development; Schizophrenia; Sensory perception; Stem cells; Study Protocol; Substance abuse treatment; Teenagers; Velocardiofacial syndrome; Young Adult
• ISSN: 1471-244X; 1471-244X
• DOI: 10.1186/s12888-023-04888-5

22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal interstitial-deletion disorder, occurring in approximately 1 in 2000 to 6000 live births. Affected individuals exhibit variable clinical phenotypes that can include velopharyngeal anomalies, heart defects, T-cell-related immune deficits, dysmorphic facial features, neurodevelopmental disorders, including autism, early cognitive decline, schizophrenia, and other psychiatric disorders. Developing comprehensive treatments for 22q11.2DS requires an understanding of both the psychophysiological and neural mechanisms driving clinical outcomes. Our project probes the core psychophysiological abnormalities of 22q11.2DS in parallel with molecular studies of stem cell-derived neurons to unravel the basic mechanisms and pathophysiology of 22q11.2-related psychiatric disorders, with a primary focus on psychotic disorders. Our study is guided by the central hypothesis that abnormal neural processing associates with psychophysiological processing and underlies clinical diagnosis and symptomatology. Here, we present the scientific background and justification for our study, sharing details of our study design and human data collection protocol. Our study is recruiting individuals with 22q11.2DS and healthy comparison subjects between the ages of 16 and 60 years. We are employing an extensive psychophysiological assessment battery (e.g., EEG, evoked potential measures, and acoustic startle) to assess fundamental sensory detection, attention, and reactivity. To complement these unbiased measures of cognitive processing, we will develop stem-cell derived neurons and examine neuronal phenotypes relevant to neurotransmission. Clinical characterization of our 22q11.2DS and control participants relies on diagnostic and research domain criteria assessments, including standard Axis-I diagnostic and neurocognitive measures, following from the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) and the North American Prodrome Longitudinal Study (NAPLS) batteries. We are also collecting measures of autism spectrum (ASD) and attention deficit/hyperactivity disorder (ADHD)-related symptoms. Studying 22q11.2DS in adolescence and adulthood via deep phenotyping across multiple clinical and biological domains may significantly increase our knowledge of its core disease processes. Our manuscript describes our ongoing study's protocol in detail. These paradigms could be adapted by clinical re